The present invention relates generally to the treatment and nutritional support of patients. More specifically, the present invention relates to the treatment of patients suffering from intestinal wounds or ulcers or at risk of same.
An ulcer is a common inflammatory lesion in which a loss or destruction of superficial tissue exists. Ulcers occur in several locations as acute, sub-acute, chronic or recurrent types. In each location, some initiating factor, such as action of bacterial toxins or lack of oxygen, causes death of the surface tissue. This necrotic tissue then usually sloughs off, leaving the underlying area exposed to further damage.
Peptic ulcers are a common form of ulcers that occur in the upper gastrointestinal tract. Peptic ulcer is defined as a circumscribed ulceration of the mucous membrane penetrating through the muscularis mucosa and occurring in areas exposed to acid and pepsin. The loss of the mucosa, ordinarily covered by a mucous secretion, lays bare the musculo-membranous wall. Peptic ulcers occur most commonly in the first few centimeters of the duodenum (duodenal ulcers) and along the lesser curvature of the stomach (gastric ulcers). See The Merck Manual, 16th Edition, p. 768.
While the peptic ulcer continues to be a common ailment in the general population, the immediate cause of such ulcer remains unknown. Emotional tension and certain physiological patterns are frequently present in affected individuals. Many influences may disturb the balance between ulcer-promoting factors (e.g., secretion of acid or pepsin into the stomach) and factors protecting the mucosal lining of the esophagus, stomach or duodenum (e.g., mucous production, membrane barriers to permeability, and replacement of shed or damaged mucosal cells). See The Merck Manual, 16th Edition, p. 768.
Ulcerative colitis of the large intestine is similar, in many respects, to peptic ulcer, because its exact cause is also unknown. Ulcerative colitis is defined as a chronic, non-specific, inflammatory and ulcerative disease arising in the colonic mucosa and is characterized most often by bloody diarrhea. The disease usually begins in the rectosigmoid area and may extend proximally, eventually to involve the entire colon, or it may include most of the large bowel at once. See The Merck Manual, 16th Edition, p. 834.
Similar to ulcerative colitis, intestinal ulceration and stricture formation are also characteristic of the inflammatory bowel disease, Crohn's disease. Crohn's disease is defined as a non-specific chronic transmural inflammatory disease that most commonly effects the distal ileum and colon. See Merck Manual, 16th Edition, p. 830. However, it may also occur in other parts of the GI tract. The disease is common and causes inflammation of the small intestine and large bowel.
While the immediate causes for intestinal ulcers and wounds remain uncertain, such ulcers and wounds are known to be the adverse side effect of certain drug treatments. For instance, many nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastrointestinal side effects. Single or multiple ulcerations, including perforation and hemorrhage of the esophagus, stomach, duodenum or small and large intestine, have been reported in patients receiving such NSAIDs. See Physicians' Desk Reference, 48th Edition, p. 1473.
Prevalent areas subject to ulceration seem to be the stomach and small intestine. Patients who take NSAIDs have an increased risk of mucosal damage in the upper gastrointestinal tract. Many nonsteroidal anti-inflammatory drugs (NSAIDs) cause small intestinal inflammation that may lead to ulceration, perforation and death. See Bjarnason et al, Nonsteroidal Antiinflammatory Drug-Induced Intestinal Inflammation in Humans, Gastroenterology, Vol. 93, No. 3, pp. 480-489 (1987). Recent studies have shown that 70% of patients on long-term NSAIDs develop small intestinal inflammation. See Bjarnason et al, Clinicopathological Features of Nonsteroidal Antiinflammatory Drug-Induced Intestinal strictures, Gastroenterology, Vol. 94, No. 4, pp. 1070-1074 (1988). Studies have shown a link between the use of NSAIDs and serious complications of peptic ulcer disease. Allison et al, Gastrointestinal Damage Associated with the Use of Nonsteroidal Antiinflammatory Drugs, The New England Journal of Medicine, Vol. 327, No. 11, pp. 749-753 (1992).
The pathogenesis of the intestinal inflammation is incompletely understood but thought to involve several interacting factors. Increased intestinal permeability is evident within hours of NSAID ingestion. Researchers have suggested that this exposes the mucosa to luminal macromolecules and toxins. In conjunction with the effect of NSAIDs on chemotaxis and neutrophil function, this may make way for bacterial invasion and hence inflammation. Id.
In addition to small intestinal ulceration, gastrointestinal bleeding without obvious ulcer formation and perforation of pre-existing sigmoid lesions (diverticulum, carcinoma, etc.) have occurred in patients receiving NSAIDs. Researchers have also reported increased abdominal pain in ulcerative colitis patients as well as the development of ulcerative colitis and regional ileitis to occur rarely. See Physicians' Desk Reference, 48 Edition, p. 1473.
Still further, researchers have reported that ingested NSAIDs may cause a nonspecific colitis (in particular, fenemates), and many patients with collagenous are taking NSAIDs. NSAIDs may also cause relapse of classic inflammatory bowel disease and contribute to serious complications of diveticular disease (fistula and perforation). Bjarnason et al, Side Effects on Nonsteroidal Anti-inflammatory Drugs on the Small and Large Intestine in Humans, Gastroenterology, 104 (6), pp. 1832-47 (1993).
Although it is well known that NSAIDs cause or aggravate intestinal ulcers or wounds in humans, few researchers have addressed ways to prevent or reduce this adverse side effect in patients receiving such drugs. Nevertheless, NSAIDs continues to be the primary recommended drug treatment for various arthritis patients, such as patients suffering from rheumatoid arthritis, ankylosing spondylitis and osteoarthritis. As a result thereof, patients receiving such NSAIDs as a treatment for their arthritic condition often must endure the adverse gastrointestinal side effects of such drugs.
Therefore, a need exists for a method of aiding healing or preventing the onset of intestinal wounds or ulcers in a patient at risk of same.